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Physiological and Immunological Effects of Naïve and Pre-Activated Mesenchymal Stromal Cells in Klebsiella Pneumoniae-Induced Sepsis in Rats

Claire Masterson, Declan Byrnes, Hector Gonzalez, Daniel O'Toole, Sean Mccarthy, Shahd Horie, Jack Brady, John Laffey
European Respiratory Journal 2020 56: 2578; DOI: 10.1183/13993003.congress-2020.2578
Claire Masterson
1Lung Biology Group, National University of Ireland Galway, Galway (Co Galway), Ireland
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  • For correspondence: claire.mast@gmail.com
Declan Byrnes
1Lung Biology Group, National University of Ireland Galway, Galway (Co Galway), Ireland
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Hector Gonzalez
1Lung Biology Group, National University of Ireland Galway, Galway (Co Galway), Ireland
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Daniel O'Toole
1Lung Biology Group, National University of Ireland Galway, Galway (Co Galway), Ireland
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Sean Mccarthy
1Lung Biology Group, National University of Ireland Galway, Galway (Co Galway), Ireland
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Shahd Horie
1Lung Biology Group, National University of Ireland Galway, Galway (Co Galway), Ireland
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Jack Brady
1Lung Biology Group, National University of Ireland Galway, Galway (Co Galway), Ireland
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John Laffey
2Anaesthesia and Intensive Care Medicine, Galway University Hospitals, Galway (Co Galway), Ireland
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Abstract

Introduction: Bacterial infection remains the leading cause of ARDS development and death in critically ill patients. Klebsiella pneumoniae is a major cause of nosocomial and community-acquired infections globally [Moradigaravand et al., 2017]. Here we aimed to show that in a clinically relevant model of K. pneumoniae infection MSCs can attenuate multiple aspects of the injury.

Methods: Sprague Dawley rats received an intratracheal bolus of K.pneumoniae to induce pulmonary sepsis. MSCs (naïve or pre-activated) were given intravenously and 48h later animals were assessed for injury/repair. Compliance and blood gas analyses were carried out pre-mortem. Blood, bronchoalveolar (BAL) and peritoneal lavage (PL) fluids were collected and analysed for leukocyte numbers, differential cell counts, bacterial content, and phagocytic function, while inflammatory cytokine levels were quantified by ELISA.

Results: MSC administration resulted in the decrease of total BAL and PL cell infiltrates, the proportion of inflammatory cells, and K.pneumoniae bacterial load. MSC therapy also resulted in an improvement in alveolar–arterial gradient and serum lactate, but not in lung compliance.

Conclusion: MSCs are effective in K.Pneumoniae-induced sepsis, reducing lung injury and bacterial load. Their mechanism of action is largely immunological and may be enhanced by pre-activation strategies.

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  • Pneumonia
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Footnotes

Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 2578.

This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2020
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Physiological and Immunological Effects of Naïve and Pre-Activated Mesenchymal Stromal Cells in Klebsiella Pneumoniae-Induced Sepsis in Rats
Claire Masterson, Declan Byrnes, Hector Gonzalez, Daniel O'Toole, Sean Mccarthy, Shahd Horie, Jack Brady, John Laffey
European Respiratory Journal Sep 2020, 56 (suppl 64) 2578; DOI: 10.1183/13993003.congress-2020.2578

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Physiological and Immunological Effects of Naïve and Pre-Activated Mesenchymal Stromal Cells in Klebsiella Pneumoniae-Induced Sepsis in Rats
Claire Masterson, Declan Byrnes, Hector Gonzalez, Daniel O'Toole, Sean Mccarthy, Shahd Horie, Jack Brady, John Laffey
European Respiratory Journal Sep 2020, 56 (suppl 64) 2578; DOI: 10.1183/13993003.congress-2020.2578
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